SU1447282A3 - Method of producing derivatives of 4 beta-(1- prime-alken-1- prime-yl)-2- xy, 5 alpha-dihydroxy-3,3a beta,4,5,6,6a beta-hexahydro-2h-cyclopent (b) furan - Google Patents

Abstract

The invention relates to heterocyclic compounds, in particular to the preparation of derivatives of 4j5- (l -alkene--1 -yl) -2.5 o-dihydroxy-3, 3a (4,6,6, 6a (1-hexahyd o -2H-cycl openta (b) Fura of formula (1) 5 OZ, 0-1, cf where either an alkyl or a protecting group such as a trialkylsilyl or tetrahydropyranyl group, X is an alkenyl group C-f-Cg, optionally substituted by a methyl or phenyl group and / or hydroxy group which may be protected by trialkylsilyl or tetrahydropyranyl groups which are intermediates in the synthesis prostaglandin. The goal is to develop a process for the preparation of new compounds. They are obtained from a compound of formula (I), where Zi is only methyl-, Z, is indicated above, in addition to H and butyl lithium, in the presence of boron trifluoride in and then introduced into interaction with an electrophilic reagent of the formula R, -CO-R, where R, is H, R, is a lower alkyl group, optionally substituted by an OH group, which can be protected by trialkylsteel or tetrahydropyranyl groups or, group, followed by restoration of the product obtained by sodium amalgam in methanol and removing the protective groups by the action of aqueous acetonitrile in the presence of a strong inorganic acid. O) 4 4 ;; vi to 00 to

Description

one

This invention relates to a new method for the preparation of 4pi- (l-al-ken-1-yl) -2, 5o-dihydroxy-3, fi, 4,5,6,6a p-hexahydro-2H-cyclopenta (b) furan derivatives formulas

CH

fOZ.

z, o

i

.Xx

(I)

where Z is hydrogen or alkyl}

Z is hydrogen or a protective corpse, such as a trialkyl or tetragichiro pyranyl group,

important intermediates in the synthesis of prostaglandins, in particular prostaglacidine,

The purpose of the invention is to create a new method of obtaining key intermediate products of formula (I) for the synthesis of prostaglandins, which is a simple, technological process with an increased yield of target products.

In examples 1-10, formulas 1-7 are given.

HE

soon

he

1L

but

he

Formula 1 Activation O

 /

2. R-C-R formulas

P

; t h

SNGZOGAg 20

formula 3,

 .-. Y

ACH-B v

-sn-in

Z O ArSOj

sun night

Formula 5 Formula - С H2

° -

SNS

formula 6

sn,

sn (he) sn

X

/

N

with hi

about

(0.12 ml, 1 mmol), and after the next 10 minutes, 2- (t-butyldimethylsilyloxy-) (Formula 4, R H, - R z CH- (t-C4H9) (CH3) i (260 mg, 1 mmol), the temperature of the reaction mixture was kept at -18 ° C for 1.5 h, and this temperature was kept at 10 ° C for the next

16 hours. After this time, a solution of ammonium chloride in tetrahydrofuran is added, and the mixture is extracted with methylene chloride (ml).

15 and the combined extracts were washed with brine, dried (MgSO4), the solvent being evaporated. A crude 4 / 3- (1 - (benzenesulfonyl) -2 -hydroxy-3 - (t-butyldimethyl s20yloxy) -o-octyl1o) (y-butyl-dimesh1sil10xi) -2 -methoxy-3 is obtained. , 5,6,6a / -hexagid ro-2H-1ccclopenta (b) furan (formula 5, Ar, B -CH (OH) CH (OSitt-C4H5) (CH3) 2) 25 -slc ,, SNOSNz, g Si () g (CH3))

(990 mg), which is dissolved in

methanol (8 ml) and process

in an argon atmosphere with 6% sodium amalq gum (5 g) for 2 hours.

30 The clear solution is decanted from wasps; tal amalgam is diluted with water at a temperature and extracted with benzene. The organic extract is washed with a saturated sodium chloride solution (brine) and dried (), after which the solvent is extracted under reduced pressure. Obtain the target compound (600 mg, - 80%) in the form of a thick syrup; spectrum

40 N NMR (ppc): 5.5 (m, 2H, vinyl protons) i 5.1. (M IH,) i 4.9-3.4 (m, 4H); 3.25 (p, 5, 3N, OCH3) v 0.9 (S, 18H, Si — C — CH) 0.85 (p, 3N;

go

cm / CH,

CH

45

one

CHj).

The analytical sample is distilled at (0.2 mm Hg)

formula 7

Example 1. In a solution of rac 4 /} - - (benzolylphenylmethyl) -5of (t-butyl-dimethylsilyloxy) -2-5-methoxy-3, 4,5,6, 6a | g-hexagicro-2H-cyclopenta (b ) furan (formula 3 Ar, Y CH-OCHj, Z Si () (CH),) (427 mg, I mmol) in tetrahydrofuran (5 ml), stirred under argon at -70 ° C, was added n- butyl lithium (1.4 M in hexane, 0.7 ml, I mmol). After 3 minutes, boron trifluoride etherate is added.

H NMR (ppm): 5.5 (m, 2H, vinyl protons) i 5.1. (M IH,) i 4.9-3.4 (m, 4H); 3.25 (p, 5, 3N, OCH3) v 0.9 (S, 18H, Si — C — CH) 0.85 (p, 3N;

CH

one

CHj).

Analytical Trial Dis

tilirut with (0.2 mm Hg)

Calculated,%: C 65.56; H 11.01,

CjgHj O Si j (512.9)

Found,%: C 65.72- H, 11.29.

Example 2. Preparation of 4p- (l - -oocten-1-mi) (t-butyldimethylsilyl-oxime) -2-methoxy-3, 3a (h, 4.5, 6.6a / 5-hexahydro-2H-csh loop (b) furan (formula 2, X —CH, Y CHOCHj, Z Si (t-C4Hg) (CHj), j).

The operations are the same as in Example 1 until the addition of boron trifluoride etherate and then hepthial (Formula 4, RH, Rj) (130 mg, 1.1 mmol) is added dropwise over 10 minutes. The temperature of the reaction mixture is raised to within 1.5 h, and this temperature is maintained for 16 h. At the end of this time, a solution of ammonium chloride in tetragncrofuran was added and the mixture was extracted with methylene chloride (ml). The combined extracts are washed with brine, dried (MgSO4) and the solvent is then steamed under reduced pressure. Prepared with 4 /} - (1 - (benzenesulfone) -2-hydroxy-1 -octyl) -5of- (t-butyldimethyl) or -3.3ar, 4,5,6,6a-hexahydro-2H- -cyclopenta (b) furan (formula 5, Ar, B -CH (OH), Y CHOSH3 Z Si (tq, Hj) (CH3) j,) (700 mg), which is dissolved in methanol (5 ml) and processed under argon atmosphere, 6% sodium amalgam (3 g) for 2 hours. The clear solution is decanted from the remaining amalgam, diluted with cold water and extracted with benzene. The organic extract is washed with brine and dried (MgSO4), and then the solvent is extracted under reduced pressure. A crude target compound (480 mg, 96%) was obtained in the form of a thick syrup; spectrum n MMR (ppm): 5.5 (m, 2H, vinyl protons) g 5.2 (m, 1H; C, j-H) 3.25 (p, s, 3N, OCHj); 0.9 (s, 9H Si — C — CH). Analytical samples distilled at (1 mm Hg)

Calculated,%: C 78.95; H 12.65.

 (334.6)

Found,%: C 78.80; H 12.82. Example 3. Getting 4 | i- (2 - -phenylene-1 -yl) (1-butyldimethylsilyloxy) 2 5-methoxy-3, Zar, 4,5,6,6a | 5- -hexahydro-2H-cyclopent (B) furan (formula 2, X —CH, Y CHOCHj, Z Si (t-C4H9) (CH3)).

The operations are the same as in Example 1 until the addition of boron trifluoride etherate and then after 10 minutes benzoaldehyde (formula 4, RH,; Cg CfeHj) (110 mg, 1.1 mmol) is added dropwise. The temperature of the reaction mixture increased to within 1 h, and this temperature was held for 8 h. After this, a solution of ammonium chloride in tetrahydrofuran is added and the mixture is extracted with chlorine-Tbw with methylene. The combined extracts are washed with brine, dried (MgSO4) and solvent diluted under reduced pressure. A crude 4fj- (1 -benzenesulfonyl) -2 f- -hydroxy-2-phenyl-1 -3Tmi-5o (- (t-6y-dimethylsilyloxy) -2-methoxy-3 is obtained,

(O Over / 3,4,5,6,6ar-hexahydro-2H-cyclo-penta (b) furan (formula 5, Ar, B —CH (OH) SbH5, Y SHOUS, Z Si (t-CfE -) (CE)) (500 mg), which is dissolved in methanol. (5 ml)

15 and treated under argon with 6% sodium amalgam (3 g) for 3 hours. The clear solution is decanted from the remaining amalgam, diluted with cold water and extracted with benzene. The organic extract is washed with brine and dried (MgSO4), after which the solvent is evaporated under reduced pressure. The desired compound is obtained in the form.

25 thick syrup. The assay is chromatographed and dried under high vacuum.

Calculated,%: C, 70.54 H, 9.15.

0 C ,,, H ,, Oz51 (374.6)

Found,%: C, 70.30- H, 9.20. Example 4. Obtaining (2- -phenylethyn-shl) (t-butyldimethylsilyloxy) -2-methoxy-3, Over / 3,4,5,6,

-jc 6a / 1-hexahydro-2H-cyclopenta (b) furan.

To a solution of rac 4 / - (benzenesulfonylmethyl) -5 ° C- (1-batch 1 dimesh1 Silsh 10 x) - -2-methoxy-3, Over / 3,4,5,6, 6a / 3-hexahyd0 ro-2H-cyclopenta (b ) furan (formula 3 Ar, Y CH-OCH3, Z Si (t-C4Hc,) (CHj)) (427 mg, I mmo.g1) in tetrahydrofuran (25 ml), stirred at -78 C, in an atmosphere of argon gon n-butyl lithium (1.4 M in hexane, 0.8 ml, 1.1 mmol) is added, and then benzoaldehyde (120 mg, 1.1 mmol) is added dropwise. The reaction mixture is held at -60 ° C for

Qeing for 3 hours, then left at

room temperature at 16h. At the end of this time, a saturated aqueous solution of ammonium chloride (0.5 ml) is added, the mixture is extracted with

5 methylene chloride (3x10 ml), the combined extracts are washed with brine and dried (MgSO4). After evaporation of the solvent under reduced pressure, crude 4fV- (l-benzene sulfonyl) -2 f-hydroxy-2-phenyl-ethyl-5 ° (- (t-butyldimethylsilyloxy) -2-methoxy-3, Zar, 4.5 , 6, ba / l-hexa-hydro-2H-cyclopenta (b) furan (Formula 5, Ar "CfH ,,,, B -SHSONUS H, Y - SNOSH, Z Si (t-C4H9) (CH3) i) which is purified by chromatography on silica gel using a mixture of hexane and ethyl acetate (3: 1) during elution.The purified product (399 mg, 75%) reveals an absorption maximum at 3500 cm in the infrared region of the spectrum. (film) and in the NMR spectrum

in infrared

«« КС

3500

(OH), 1300 and 1125 (), 1250 and 1260 (CHjSi iPS4% 81), 1110-1050 (C-O-C, C-0-Si) cm. Spectrum HNMR (CDCle), (ppm) :; 8, 00-; 7.31 (m, 5H, aroma, H) 5.10 (m, 1H, CiH) -, 4.51 (m, 1H, cjH) - 4.11 (m, 1H, C H); 2.85 (m, 1H, C, H); 1.61

and

1.63 (two singlet, 3N, SiCHj); 0.74 (s, 9H, SiCCHj).

The product described is dissolved in methanol (2 ml) and treated with sodium amalgam (6% Na) under ar- the following signals; (CDCyppm: 0.85 (t, 15 gon at room temperature in te9H); 1.0-2, 7 (m, OH), 3.21 (8, 3N);

3.95-4.25 (m, 1H); 5.0-5.2 (m, lH) j 7.1-8.2 (m, yun),

This product was dissolved in methanol (5 ml) and treated under argon with 6% sodium amalgam (3 g) i for 3 hours. The clear solution was decanted for a remaining 14 hours. After this time, the solution was decanted from the amalgam residues, diluted with hexane (30 ml), washed with saturated ammonium chloride solution and brine, dried (MgSOvf) and the solvent evaporated under reduced pressure. The residue (84 mg) is chromatographed on silica gel (2 g) with an eluence of 14 hours. After this time, the solution is decanted from the amalgam residues, diluted with hexane (30 ml), washed with saturated ammonium chloride solution and brine, dried (MgSOvf) and the solvent evaporated under reduced pressure. The residue (84 mg) is chromatographed on silica gel (2 g) using elugam, diluted with cold water and extracting a mixture of toluene and hexane to be traced with benzene. Organic extract ratio 4: 1.

The wash is washed with brine and dried. The desired product is obtained (72 mg) (MgSO4), after which the solvent is extracted in the form of oil, the spectrum is infrared under reduced pressure. VMOKC 1450 (С С) j 1260, the target compound is obtained (150 mg) 30 1250 (СНэ51, пС4Н951), 1170, 1150, identical to that described in example 3. OK (С С, Si-0) cm H

PRI me R 5. Getting 4p- (2 -

-methyl-1 -oocten-G-yl) (: - butyldi-; Spectrum HNMR (CDClj), (ppm): 0, OO methylsilyloxy) -2-methoxy.-3, Z / A, 4,5,6 , (m, 9H, -cCHa) j 1.68 (m, ЗН, С C-CHj), 6а / Ь-hexahydro - 2H-cyclopenta (b) fura- 35 29 (s, ЗН) -ОСНз); 3.69 (n, on (formula 2, X —CH C (CH h); 1H, CuI) 4.41 (m, 1H,) - 4.80 Y. SHNOS, Z-Si (t-C4H3) ( CH3)). (m 1H, С СН); 5.07 (m, 1H, C, H). The operations are the same as in the example: Mass spectrum with a high degree of division 1, until the addition of the fission ester to calculate boron trifluoride, and then after 40 m: 396.3060; Neutrovented octa-396.3060 is added dropwise for 10 minutes.

non-2 (128 mg, 1 mmol) Temperature Example 6. Preparation of (3,. the reaction mixture is boiled to + 20 ° C. Isopropylidenedioxy-l-butene-1 - for about 1 h and ras-yl is added) (t -butyldimethylsilyloxy) thief of ammonium chloride in tetrahydro-45 methoxy-3,3ar "4,5,6,6a -hexigropo-2H-cyclopenta (b) of furan (formula 2, X group with formula 6, Y CHOCHj, Z Si, (t-rqH (CH3)).

The operations are the same as in Example 5Q Pe 1, until the addition of boron trifluoride etherate, and then after 10 mIn the solution (S) of 0.0-isopropylidene glyceraldehyde (162 mg, 1.25 mmol ) in benzofuran. The resultant was diluted with chloroform (50 ml), washed with brine, dried (MgSO4) and the solvent evaporated under reduced pressure. The residue (520 mg) is chromatographed on silica gel using chloroform for elution. 4r- (1- - (benzenesulfonyl) -2 -hydroxy-2 - -methyl-1 -octyl) -2-methoxy-3, 3a are obtained (s, 4

5,6,6a | b-hex agidro-2H-cyclopenta (b) 55 ml). The reaction mixture vsherfuran (formula 5, Ar C / And

AT

 -C (OH) (CH3) -nC (Hij, Y CHOCHg, Z Si () (CH) 2) (170 mg, 30%), revealed the following properties: spectrum

live for 2 hours and then the temperature is raised to 0 ° C in those. - 1 hour. After this time, add a saturated aqueous solution of infrared

«« КС

3500

(OH), 1300 and 1125 (), 1250 and 1260 (CHjSi iPS4% 81), 1110-1050 (C-O-C, C-0-Si) cm. Spectrum HNMR (CDCle), (ppm) :; 8, 00-; 7.31 (m, 5H, aroma, H) 5.10 (m, 1H, CiH) -, 4.51 (m, 1H, cjH) - 4.11 (m, 1H, C H); 2.85 (m, 1H, C, H); 1.61

and

1.63 (two singlet, 3N, SiCHj); 0.74 (s, 9H, SiCCHj).

The product described is dissolved in methanol (2 ml) and treated with sodium amalgam (6% Na) in an argon atmosphere at room temperature for 14 hours. After this time, the solution is decanted from the amalgam residues, diluted with hexane (30 ml), It is saturated with ammonium chloride solution and brine, dried (MgSOvf) and the solvent is evaporated off under reduced pressure. The residue (84 mg) is chromatographed on silica gel (2 g) using a mixture of toluene and hexane for a 4: 1 ratio for elution.

5 ml). The reaction mixture is held for 2 hours, and then the temperature is raised to 0 ° C for 1 hour. At the end of this time, add a saturated aqueous solution of aMMOHHJf chloride (0.5 ml), extract the mixture with methylene chloride (ml), the combined extracts are washed & brine and dried (MgS04). The solvent is entrained and the residue (620 mg) is chromatographed on a sklicagel column (60 g) with

-2-methoxy-3, Zar, 4.5, 6.6a / -hexahydro-2H-cyclopenta (b) furan (formula 2, X -CH-CH-CH (OSi () (CH3)) - 5, ,, Y CHOCHj, () (CHpj).

According to the method described in Example 1, 4p- (I-benzene sulphonyl) 2 is obtained - by using for the elution a mixture of hex-hydroxy-3 - (t-butyldimethylsilyl-ssilane and ethyl acetate in a ratio of 3: 1. Hydroxy) -2-methoxy- 3.3a / J, 4,5,6, bar-hexahydro-2H-cyclopenta (b) furan (formula 5, Ar, B CH (OH) CH (OSi (t-C4H9) (CH3), t); , Y SNOSNz, Z-Si (t-C4Hg) (C Hp,) 15

There is obtained (3,4-isopropylidenedioxy-2-hydroxy-1 - (benzenesulfonyl) -but-1 -yl) -5a - (1-butyldine-thylsilyloxy) -2-methoxy-3, Zar, 4,5, 6,6a / 5-hexahydro-2H-cyclopenta (b) furan (formula 5, Ar, B group with formula 7, Y is CHOCH,, Z

l /. J-h / / / P /: "

To a solution of the above compound (671 mg, 1 mmol) in pyridine (15 ml), stirred under an atmosphere of

Si (t-C4H5) (CH3)) (484 mg) in the formargonone, at a temperature of - 10 C to a colorless oil; 3400 (OH) cm-1 methanesulfonyl chloride (0.3 ml,

In the solution of the above indicated compound (204 mmol) and the mixture is kept for 16 hours

nor (426 mg, 1 mmol) in tetrahydro-at. Then the reaction mixture

furan (2.5 ml), stirred in at-concentrate to about 1/5 of the volume.

argon in the atmosphere, at -78 ° C, n-butyl lithium is added (1.4 M in hexane, 1.1 mmol)

Stirring is continued for 30 minutes, after which benzoyl chloride (0.126 ml, 1.09 mmol) is added. The mixture is heated to room temperature in terazabavl toluene (10 ml) and washed with chilled 3% hydrochloric acid 25, brine, and with an assessment solution of NaHCO-c. The solution is dried with MgSO4 and the solvent is evaporated. The residue (700 mg) is chromatographed on

silica gel (10 g), eluting for 3 h, 3- (dimethylamine-30 mixtures of toluene and ethyl acetate 98: 2. but) -1-propylamine (0.1 ml) are added, and then methanesulfonate (600 mg, 80% ),

This compound is dissolved in absolute methanol (7 ml), and in a solution stirred under an Arlon atmosphere with a mixture of hexane and ethyl acetate 3: 1 gives the benzoyl derivative in the form of a colorless oil (500 mg). This

do and extract with methylene chloride (Evil ml). The combined extracts are dried (MgSO4), the solvent is evaporated, and the residue is applied to 35 g of it, and a powdered silica gel is added. Intrusion to - (660 mg). The mixture is cooled to -40 ° C and 6% sodium amalgam (2.2 g) is added in portions over about 30 minutes. The cooling compound is dissolved in a tetrahydrofluoric bath and removed and then reached a rage (6 ml), under argon atmosphere, and 6% sodium amalgam is added to the reaction mixture at room temperature (about 1 hour). 1 g) and after cooling the mixture to a saturated solution of ammonium chloride -20 ° C methanol (2 ml). Received (3 ml), and then water. The mixture is extra-stirred for 3 hours at -20 ° C. After 45 ml of toluene (ml), at the same time, saturated extracts are added to dry: MgCO and the aqueous solution of ammonium chloride is evaporated under reduced monomer (0.5 ml), water and an extraordinary mixture. pressure. The residue (415 mg) was chromatographed with methylene chloride (3x10 ml). mapped on silica gel (10 g) with

50 by elution with a 98: 2 mixture of toluene and ethyl acetate. Obtained target compound (344 mg, 85%), identical with ethanol.

Example 8. Preparation of 4pi- (2-6: 1. The expected product is obtained (180 mg of 55-phenylene-l-yl) -5 (((t-butyl-dimethyl-52%), identical with ethanol. Silshloxy) 29-methoxy- 3, Zar-4,5,6,

Example 7. Preparation of 4p) - (3 - 6ar-hexahydro-2H-cyclopenta (b) fu- - (1-butyldimethylsilyloxy) -H-octane. (Formula 2, X-CH-CH -, -1 -yl ) -5o / - (t-butildimethylsiloxyls) - Y СНОНз, Z Si. (T-C4.Hg) (СН)).

The combined extracts are dried (MgSO4), the solvent is evaporated and the residue is chromatographed on a silica gel column using a mixture of hexane and ethyl acetate for elution.

-2-methoxy-3, Zar, 4.5, 6.6a / -hexahydro-2H-cyclopenta (b) furan (formula 2, X -CH-CH-CH (OSi () (CH3)) - 5, ,, Y CHOCHj, () (CHpj).

sagidro-2H-cyclopenta (b) furan (formula 5, Ar, B CH (OH) CH (OSi (t-C4H9) (CH3), t);,, Y СНОНз, Z-Si (t-C4Hg) (C Hp,)

To a solution of the above compound (671 mg, 1 mmol) in pyridine (15 ml), stirred under an atmosphere of

diluted with toluene (10 ml) and washed with chilled 3% hydrochloric acid 25, brine, and a high-grade solution of NaHCO-c. The solution is dried with MgSO4 and the solvent is evaporated. The residue (700 mg) is chromatographed on

According to the method described in Example 3, 4/3 - ((benzenesulfonyl) -2-hydroxy -2-phenyl-ethyl-5rf- (t-butyldimethylsilyloxy) -2-methoxy-3, 3a / is obtained. s, 4,5,6, 6a / 3-hexahydro-2H-cyclopenta (b) furan (formula 5,

, B-CH (OH), Y "SHUTTER ,,

Ag Z

6ar-hexahydro-2H-cyclopent (b) furan, prepared as in Example 1, (197 mg, 0.4 mmol), is dissolved in a mixture of acetonitrile and water (2: 1, 2 ml), hydrochloric acid is added and the mixture is left at room temperature for 16 hours. The mixture is then concentrated under reduced pressure, toluene is added and the organic layer is separated. The aqueous layer was extracted with toluene (ml). The combined organic extracts are washed with brine, dried (MgSO4) and the solvent evaporated under reduced pressure. The residue (150 mg) was applied to a column of silica gel (12 g) and the column was washed with a mixture of toluene - chloroform - methanol (10: 5: 1), and a yield of 10% was obtained.

Si (t-C4Hj) (CH: j), j) (500 mg). To a solution of the above indicated compound (475 mg, 0.89 mmol) and 1.10 phenanthrolein (1 mg) in tetrahydrofuran (3 ml), stirred at -78 s, under argon atmosphere, is added 1 M in hexane) until the appearance of a dark color. After 30 minutes, benzoyl chlorinates (0.13 ml, 1.112 mmol) are added dropwise, the mixture is cooled in a bath until it reaches room temperature (for 3 hours), 20 left product (97 mg, 90%). Sector IR Then 3- (dimethylamino) -1-max-3350 (OH) is added; 1650 (C C); 1100-propylamine (0.1 ml), the mixture is diluted with water and extracted with methylene chloride (3x10 ml)., The United extracts are dried (MgSO4), the solvent is extracted, and the residue is applied to a 400-mesh silica gel. The column is washed with a mixture of hexane and ethyl acetate (5: 1) and the solvent is forced in, the benzyl derivative is obtained in the form of a colorless oil (550 mg). This product is dissolved in tetrahydrofuran (6 ml), under argon atmosphere, 6% sodium amalgam (1 g) is added.

max 1000 (C-0) cm-.

NMR spectrum: 3.95 (m, 2H, SNON) 4.42 (m, 1H,); 5.28 (m, 1H,); 25 5.55 (m, 2H, С СН).

Example 10. Preparation of prostaglandin F (formula 1). The compound obtained in Example 9 (97 mg, 0.36 mmol) was dissolved in dimethyl-30 sulfoxide (1 ml) and the solution was added to a solution of ylide prepared as follows: a solution of sodium salt of dimethyl sulfoxide (dimsyl sodime) in dimethyl sulfoxide (1.7 M,

the dropwise mixture is cooled to and then to 35 ml, 2 mmol)

Methanol (2 ml) was added. Stirring is continued in a solution of triphenyl bromide at -20 ° C. For 3 h, after which (4-carboxy-butyl) phosphonium (443 mg, a saturated aqueous solution of 1 mmol) in dimethyl sulfoxide (1 ml of ammonium chloride (0, 5 ml). The reaction is obtained. The mixture is stirred for 1 hour while the room mixture is diluted with water and an extra-40 ° C temperature and 1 hour at 50 ° C.

6ar-hexahydro-2H-cyclopent (b) furan, prepared as in Example 1, (197 mg, 0.4 mmol), is dissolved in a mixture of acetonitrile and water (2: 1, 2 ml), hydrochloric acid is added and the mixture is left at room temperature for 16 hours. The mixture is then concentrated under reduced pressure, toluene is added and the organic layer is separated. The aqueous layer was extracted with toluene (ml). The combined organic extracts are washed with brine, dried (MgSO4) and the solvent evaporated under reduced pressure. The residue (150 mg) was applied to a column with silica gel (12 g) and the column was washed with a mixture of toluene - chloroform - methanol (10: 5: 1), and a yield of 10% was obtained.

20 left product (97 mg, 90%). IR max - 3350 (OH); 1650 (C C); 1100 product (97 mg, 90%). IR max - 3350 (OH); 1650 (C C); 1100 max 1000 (C-0) cm-.

NMR spectrum: 3.95 (m, 2H, SNON) 4.42 (m, 1H,); 5.28 (m, 1H,); 5.55 (m, 2H, С СН).

Example 10. Preparation of prostaglandin F (formula 1). The compound obtained in Example 9 (97 mg, 0.36 mmol) was dissolved in dimethyl sulfoxide (1 ml) and the solution was added to a solution of ylide prepared as follows: a solution of sodium dimethyl sulfo oxide (dimsyl sodime) in dimethyl sulfo oxide (1.7 M,

add 2 ml (2 mmol) dropwise

It is washed with methylene chloride (340 ml), the United extracts are dried (MgSO4), dissolved / evaporated, and the residue is chromatographed on a column of silica gel using a mixture of hexane and ethyl acetate for elution (I 5: 1). Get the target product (178 mg) in the form of a colorless oil, identical with the original ethanol.

Example 9. Preparation of 4p- (3 - -hydroxy-l -ogen-1 -yl) -2s (, hydroxy-3, Za (b, 4,5,6, ba / 3-hexahydro-β-cyclopent (b ) furan (formula 2, X —CH — CH (OH) —C5. H, 1, Y CHOH,., Z H).

4, p- (3 - (C-Bugyldimethylsilyloxy) -1 -1 octane-yl) -5a / - (t-butyldimethylsilyloxy) -2 ° (methoxy-3, Over / 5,4,5,6 ,

then diluted with water (5 ml) and extracted with ethyl acetate (ml). The aqueous layer was acidified with dilute hydrochloric acid and extracted with ethyl acetate (ml). The combined organic extracts are washed with brine, dried and the solvent is evaporated off under reduced pressure. The residue (500 mg) was applied per column.

with silica gel (0.0–0.08 mm Merck, 25 g) and the column was eluted with a mixture of toluene – chloroform – methanol 17: 5: 2, and rats 15-epi-PGF2 (30 mg) and rats PGF were obtained (28 mg), identical with ethanol.

Thus, the proposed method allows to obtain the target products in a technologically simplified manner.

by eliminating the Vit Vitig reaction in yields up to 36%.

Formula inventions

. The method of obtaining derivatives of 4p- (| -alken-1 -yl) -2, 5o-dihydroxy-3, 3 5/5, 4, 5,6,6a / 3-hexahydro-2H-cyclopenta (b) furan general formula

,

z, o

, SS:

Zi Z,

hydrogen or C, -CJ-alkyl, hydrogen or a protective group such as a trialkylsilylium or a tetragndropyranyl group, X is an alkenyl group g possibly substituted by a methyl or phenyl group and / or an hydroxy group that can be protected by a trialkylsilyl or a tetragypraniranyl group, likened by the fact that the phonyl derivative of a common form

-

Where

Zj

,P

14

osnz

has the indicated values, in addition to Z-hydrogen, is subjected to reaction with butyllithium in the presence of boron trifluoride in an inert organic solvent medium, and then with an electroplating reagent of the general form

15

R - CO - R

g

where R is hydrogen,

R is a lower alkyl group,

possibly substituted by a hydroxyl group which may be protected by a trialkylsilyl or tetragvodopyranyl group, hydrogen 1

a phenyl group, followed by reduction of the product obtained by sodium amalgam in methanol and removing the protective groups by the action of aqueous acetonitrile in the presence of a strong inorganic acid.

or R, - RO

Claims (1)

Claim . The method of obtaining derivatives of 4 / 3- (1'-alkene-1 '-yl) -2 £, 5Y-dihydroxy-3, Zar, 4,5,6,6a / 3-hexahydro-2H-cyclopenta (b) furan total formulas where Zj - has the indicated meanings, in addition to Z2 - hydrogen, they are reacted with'butyl lithium in the presence of boron trifluoride in an inert organic solvent, and then with an electrophilic reagent of the general form R _t - CO - R ^, where Z ₂ is hydrogen or C, -C _? -alkyl Z is hydrogen or a protective group, such as a trialkylsilyl or tetrazzo-20 pyranyl group, X is an alkenyl group C ^ -C g, possibly substituted by a methyl or phenyl group and / or an oxy group, which can be protected by a trialkylsilyl or tetrahydrodistyranyl group, characterized in that the sulfonyl derivative of the general formula 30 where R _f - hydrogen R ^ is a lower alkyl group, possibly substituted by a hydroxyl group, which may be protected by a trialkylsilyl or tetrahydropyranyl group, or R, is hydrogen R _g is a phenyl group, followed by reduction of the resulting product with sodium amalgam in methanol and the removal of the protective groups by the action of aqueous acetonitrile in the presence of a strong inorganic acid.